NIH Clinical Research Studies

Protocol Number: 03-C-0218

Active Accrual, Protocols Recruiting New Patients

Title:
Open-Label, Intravenous to Oral Switch, Multi Dose, Multi-Center Study to Investigate the Pharmacokinetics, Safety & Tolerability of Voriconazole in Hospitalized Children Aged 2 to Less Than 12 Yrs who Req Tx for the Prev of Systemic Fungal Infection
Number:
03-C-0218
Summary:
Children with a decreased ability to fight infection are at high risk for developing fungal infections. At present there are few medicines for treating fungal infections in children. Voriconazole is a new drug that is FDA approved to treat fungal infections in adults.

The purpose of this study is to determine the safety, tolerability and pharmacokinetics (the body's handling of the drug) when it is given intravenously and orally to children younger than 12.

Thirty-six children younger than 12 will participate in this study. Study participants will undergo the following evaluations: a physical exam, including an eye exam and an electrocardiogram; blood tests; and urinalysis.

Participants will receive one or more different dosages of voriconazole intravenously, depending on when they enroll in the study. At the end of IV therapy, they will receive the drug as an oral solution two times a day. Investigators will obtain blood samples from participants on day 4, 8 and 12.

Participants will remain hospitalized through day 8 of the study. On day 12, participants will undergo repeat evaluations from the beginning of the study. Their participation in this study will be last up to a maximum of 30 days. There will be two follow-up visits: at one month and at one year.

Sponsoring Institute:
National Cancer Institute (NCI)
Recruitment Detail
Type: Active Accrual Of New Subjects
Gender: Male & Female
Referral Letter Required: No
Population Exclusion(s): None

Eligibility Criteria:
INCLUSION CRITERIA:

a. Children aged from 2 to less than 12 years who require treatment for the prevention of systemic fungal infection, and who can tolerate being switched to oral therapy between Days 9 and 20 in Cohort I and II A, or Days 5 to 20 in Cohort IIB.

b. Children who are expected to develop neutropenia (ANC less than 500 cells/mm(3)) lasting for more than 10 days following chemotherapy for of the following conditions:

i. Leukemia

ii. Lymphoma

iii. Aplastic Anemia

iv. As the preparative regimen for bone marrow or stem cell transplantation.

c. Patients who are anticipated to live more than 3 months.

d. Females of childbearing potential (post-menarchal) must have a negative pregnancy test at entry.

e. Informed consent of the parent or legally authorized representative must be obtained prior to entry.

f. Assent will be obtained from minors capable of understanding.

EXCLUSION CRITERIA:

a. Patients who are receiving and cannot discontinue the following drugs at least 24 hours prior to study start or if they need to commence any of the following during the study: terfenadine, pimozide, quinidine, astemizole, and cisapride (due to the possibility of QTc prolongation with these drugs) and omeprazole (an inhibitor of CYP2C19, CYP2C9, and in lesser extent CYP3A4 isoenzymes) which is known to increase plasma voriconazole levels and ergot alkaloids.

b. Patients who have received the following drugs within 14 days prior to study entry: rifampicin, rifampin, rifabutin, carbamazepine, phenytoin, nevirapine and long acting barbiturates as these are inducers of hepatic enzymes and may result in undetectable levels of voriconazole.

c. Patients who have received sirolimus, as voriconazole is known to increase significantly sirolimus blood levels.

d. Severe hypokalemia (less than 3.2 mmol/L). Potassium may be corrected to a level greater than 3.2 mmol/L to enroll patient onto study.

e. Patients who are taking or are likely to receive any investigational drugs except those used for treatment of a child's cancer, antiretroviral agents and drugs used for treatments of any AIDS defining opportunistic infections, all of which are allowed.

f. Patients who are enrolled in investigational anticancer drug trials that exclude the use of other investigational agents should not be enrolled in this study.

g. Patients with a history or hypersensitivity to or severe intolerance of azole antifungal agents.

h. Patients who have already been entered onto this voriconazole protocol once.

i. Patients with a medical history or current evidence of cardiac arrhythmia.

j. Patients with an AST, ALT or total bilirubin greater than 5 X ULN.

k. Patients with moderate and severe renal impairment (i.e., calculated creatinine clearance less than 30mL/min). Creatinine clearance will be calculated using the following equation: 0.55 X height (cm)/serum creatinine (mg/dL).

l. Any other condition which, in the opinion of the investigator, would make the patient unsuitable for enrollment.

Special Instructions: Currently Not Provided
Keywords:
Mycoses
Prophylaxis
Pediatric
Candida Species
Aspergillus Species
Recruitment Keywords:
Pediatric
Neutropenia
Leukemia
Lymphoma
Aplastic Anemia
Fungal Infection
Conditions:
Neutropenia
Leukemia
Lymphoma
Aplastic Anemia
Investigational Drug(s):
Voriconazole
Investigational Device(s):
None

Contacts:
Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citations:
Pizzo PA, Robichaud KJ, Gill FA, Witebsky FG. Empiric antibiotic and antifungal therapy for cancer patients with prolonged fever and granulocytopenia. Am J Med. 1982 Jan;72(1):101-11. No abstract available. PMID: 7058815

Francis P, Lee JW, Hoffman A, Peter J, Francesconi A, Bacher J, Shelhamer J, Pizzo PA, Walsh TJ. Efficacy of unilamellar liposomal amphotericin B in treatment of pulmonary aspergillosis in persistently granulocytopenic rabbits: the potential role of bronchoalveolar D-mannitol and serum galactomannan as markers of infection. J Infect Dis. 1994 Feb;169(2):356-68. PMID: 8106769

Lee JW, Amantea MA, Francis PA, Navarro EE, Bacher J, Pizzo PA, Walsh TJ. Pharmacokinetics and safety of a unilamellar liposomal formulation of amphotericin B (AmBisome) in rabbits.

Antimicrob Agents Chemother. 1994 Apr;38(4):713-8. PMID: 8031034

Active Accrual, Protocols Recruiting New Patients

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